Implantable fluid delivery devices, systems, and methods

ABSTRACT

Devices, systems, and methods for delivering fluid are provided. Devices include a housing configured for intravaginal deployment and retention, at least one reservoir configured to contain a fluid, and a fluid dispensing mechanism configured to dispense the fluid past the cervix and to the uterus of the subject. Methods include intravaginally deploying and retaining a device in the subject, and dispensing the fluid from the device such that the fluid is driven past the cervix to the uterus of the subject.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.15/727,776, filed Oct. 9, 2017, which is a divisional of U.S.application Ser. No. 14/448,087, filed Jul. 31, 2014, now U.S. Pat. No.9,801,660, which are incorporated herein by reference in theirentireties.

TECHNICAL FIELD

The present disclosure relates generally to implantable medical devices,and more particularly to devices, systems, and methods for deliveringfluid to the uterus of a subject.

BACKGROUND

Medical devices may be used to deliver fluids (e.g., drugs or otherfluids) to a patient or subject. Certain devices may be configured to beimplanted at a patient site and deliver a fluid thereto. For example,intrauterine devices may be used to deliver fluids directly to theuterus of a patient, such as in an in vitro fertilization (IVF)procedure to increase the likelihood of pregnancy and/or to controlcertain aspects of a pregnancy.

However, devices that can be deployed in the uterus of a subject musthave a particular size, shape, and design, which may be difficult toachieve for certain devices and/or fluid payloads. So while devices thatare implantable in the uterus can dispense fluid, such as semen in anIVF procedure, directly to the surrounding tissue with a highprobability of fluid delivery to the uterus, it is not feasible todesign every fluid delivery device to be implanted in the uterus.

Intravaginal devices have fewer design limitations relating to thedeployment site than intrauterine devices; however, if the device canonly be placed within the vaginal cavity, dispensing a fluid to theuterus, such as semen in an IVF procedure, can be considerably moredifficult. Accordingly, there is a need for improved intravaginaldevices, systems, and methods that provide fluid delivery to the uterusof a subject.

SUMMARY

In one aspect, implantable fluid delivery devices are provided,including a housing configured for intravaginal deployment and retentionin a subject, at least one reservoir associated with the housing andconfigured to contain a fluid, and a fluid dispensing mechanism disposedwithin the housing and configured to dispense the fluid from the atleast one reservoir past the cervix and to the uterus of the subject.

In another aspect, implantable fluid delivery systems are provided,including a device having a housing configured for intravaginaldeployment and retention in a subject and a fluid dispensing mechanismdisposed within the housing; and a capsule containing a fluid to bedelivered to the subject, the capsule being configured to be insertedpast the cervix of the subject prior to deployment of the device,wherein the fluid dispensing mechanism includes an ultrasonic elementconfigured to generate an ultrasonic wave effective to rupture thecapsule and release the fluid to the uterus of the subject.

In yet another aspect, methods of delivering fluid to a subject areprovided, including intravaginally deploying and retaining a device inthe subject, the device including at least one reservoir containing afluid and a fluid dispensing mechanism; and dispensing the fluid fromthe device such that the fluid is driven past the cervix to the uterusof the subject.

In still yet another aspect, methods of delivering fluid to a subjectare provided, including inserting a capsule containing a fluid to bedelivered to the subject past the cervix of the subject; thereafterintravaginally deploying a device in the subject, the device including afluid dispensing mechanism, which includes an ultrasonic element; andgenerating an ultrasonic wave, via the ultrasonic element, effective torupture the capsule and release the fluid to the uterus of the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of an implantable fluid delivery device.

FIG. 1B is an exploded view of the implantable fluid delivery device ofFIG. 1A.

FIG. 2 is a partial cross-sectional view of one embodiment of animplantable fluid delivery device.

FIG. 3 is a partial cross-sectional view of another embodiment of animplantable fluid delivery device.

FIG. 4 is a partial cross-sectional view of yet another embodiment of animplantable fluid delivery device.

FIG. 5A is a partial cross-sectional view of yet another embodiment ofan implantable fluid delivery device having an extending member, shownin the unstressed position.

FIG. 5B is a partial cross-sectional view of the implantable fluiddelivery device of FIG. 5A, showing the extending member in the extendedposition.

FIG. 5C is a magnified partial cross-sectional view of the implantablefluid delivery device of FIG. 5B.

FIG. 6 is a partial cross-sectional view of one embodiment of animplantable fluid delivery system.

DETAILED DESCRIPTION

The devices, systems, and methods described herein meet one or more ofthe above-stated needed by provided implantable fluid delivery to theuterus of a subject. In certain embodiments, an intravaginal device isprovided that is capable of delivering a fluid past the cervix and tothe uterus of a subject.

Such devices may be particularly useful in animals, such as cattle,where the IVF procedure has to be performed by a skilled professionaland is a time-consuming, costly, and intensive procedure for eachanimal. The devices, systems, and methods disclosed herein increase thelikelihood of success of each IVF procedure by increasing the precisionof the fluid delivery. As such, the valuable sperm and the timecommitment from these professionals may be most effectively andefficiently used.

Implantable Fluid Delivery Devices and Systems

In one aspect, implantable fluid delivery devices and systems areprovided, which allow for the controlled dispense or release of one ormore fluids to the uterus of a subject. In embodiments, the release ordispense is temporally controlled, such that the fluid substance reachesthe uterus at a selected time.

In one embodiment, as shown in FIGS. 1A and 1B, an implantable fluiddelivery device 100 includes a housing 102 configured for intravaginaldeployment and retention in a subject. For example, the housing 102 ofthe device 100 may be sized and shaped for intravaginal deployment andretention in the subject. In one embodiment, the device 100 includes oneor more retention features 104, for retaining the device intravaginallyupon deployment.

For example, as shown in FIGS. 1A and 1B, depending on the fluiddispensing mechanism, and the power and actuation needs of the device,the device 100 may include a control system 114 that includes one ormore of a power source 112, a microcontroller 110, and an actuationmechanism 108. In addition, the device 100 may include a fluiddispensing system 101, which alone or in combination with the controlsystem, operates to dispense or release a fluid to the subject. Thedevice 100 may also include a fluid dispensing feature 106, such as anozzle or opening, which is associated with the housing 102. Forexample, the nozzle or opening may have a small diameter, such that thedevice is capable of delivering a thin stream or small droplets of thefluid at a high velocity.

In certain embodiments, as shown in FIGS. 2, 3, 4, and 5A-5C, the fluiddispensing system 201, 301, 401, 501 of the device includes at least onereservoir 220, 320, 420, 538 associated with the housing 202, 302, 402,502 and configured to contain a fluid, and a fluid dispensing mechanismdisposed within the housing 202, 302, 402, 502 and configured todispense the fluid from the at least one reservoir 220, 320, 420, 538past the cervix (shown as 534 in FIGS. 5A-5C) and to the uterus of thesubject. Various fluid dispensing mechanisms may be utilized in thesedevices, some of which are discussed herein. Other suitable fluiddispensing mechanisms known to those of ordinary skill in the art, ormodified versions of the fluid dispensing mechanisms disclosed herein,may also be utilized.

In certain embodiments, the fluid dispensing mechanism is an inkjet orother high-velocity fluid dispensing mechanism. For example, a thermalbubble or piezoelectric-type inkjet dispensing mechanism may beutilized. These mechanisms may advantageously propel the fluid out ofthe device at a high velocity such that the fluid is likely topenetrate, or pass, the cervix of the subject.

In one embodiment, as shown in FIG. 2 , the fluid dispensing mechanismis a thermal bubble jet mechanism, which includes a bubble jet chamber224 in fluid communication with the at least one reservoir 220, and anozzle 206 in fluid communication with the bubble jet chamber 224. Forexample, the bubble jet chamber 224 may be connected to the reservoir220 by a channel 222 or other suitable connection means. In theembodiment shown in FIG. 2 , the thermal bubble jet mechanism isconfigured to generate heat in the bubble jet chamber 224 and therebycreate a bubble of the fluid such that a droplet of the fluid isdispensed via the nozzle 206 upon expansion of the bubble.

In one embodiment, the thermal bubble jet mechanism is configured togenerate heat in the bubble jet chamber via one or more resistors. Inone embodiment, the thermal bubble jet mechanism is configured togenerate a vacuum in the bubble jet chamber 224 such that fluid in theat least one reservoir 220 is drawn into the bubble jet chamber 224 uponcollapse of the bubble.

In one embodiment, as shown in FIG. 3 , the fluid dispensing mechanismcomprises a piezoelectric jet mechanism, which includes a jet chamber324 in fluid communication with the at least one reservoir 320. Forexample, the jet chamber 324 may be connected to the reservoir 320 by achannel 322 or other suitable connection means. The fluid dispensingmechanism shown in FIG. 3 also includes a piezoelectric material incommunication with the jet chamber 324 and a nozzle 306 in fluidcommunication with the jet chamber 324. The piezoelectric material isconfigured to receive an electric charge causing it to vibrate andthereby drive fluid in the jet chamber 324 therefrom such that the fluidis dispensed via the nozzle 306.

In one embodiment, the piezoelectric jet mechanism is configured togenerate a vacuum in the jet chamber 324 such that fluid from the atleast one reservoir 320 is drawn into the jet chamber 324 upon dispenseof fluid via the nozzle 306.

In one embodiment, as shown in FIG. 4 , the fluid dispensing mechanismincludes a high velocity pump, which includes a valve 428 configured toselectively allow flow of the fluid from the at least one reservoir 420to a nozzle 406 and a pressure source 426 configured to drive the fluidfrom the at least one reservoir 420 toward the nozzle 406. In oneembodiment, the valve 428 is configured to allow flow of the fluid fromthe at least one reservoir 420 to the nozzle 406 upon generation of asufficient pressure in the at least one reservoir 420 via the pressuresource 426, such that the fluid is dispensed via the nozzle 406. As usedherein, the term “sufficient pressure” refers to a pressure that isgreat enough to drive the fluid from the intravaginally deployed device,past the cervix to the uterus of the subject.

For example, the nozzle 406 may be connected to the reservoir 420 by achannel 422 or other suitable connection means, at which a valve may belocated to regulate flow of the fluid to the nozzle. For example, thevalve may be actuated by electronics on board the device, such as thecontroller of the control system.

In one embodiment, the pressure source includes compressed gases,springs, pistons, or combinations thereof. For example, the pressuresource may include, or be associated with, an actuation mechanism 108 ofa control system 114, as shown in FIG. 1B.

In one embodiment, as shown in FIGS. 5A-5C, the at least one reservoirincludes a tube 538 extending from a gas reservoir 536 of the device,and which includes at least one gas chamber 539, 540 configured toreceive gas from the gas reservoir 536 to inflate and thereby urge thetube 538 into an extended position (shown in FIG. 5B). In oneembodiment, the at least one gas chamber 539, 540 of the tube 538 is influid communication with the fluid contained in the tube such that asthe gas chamber 539, 540 inflates, the fluid is driven out of the tube538.

For example, the tube may include an end nozzle 506 via which the fluidis dispensed from the tube 538. In certain embodiments, the fluid has asurface tension within the tube such that the fluid is not dispensedfrom the open end of the tube until a sufficient pressure from theinflation of the gas chamber(s) is applied thereto. Alternatively, theend of the tube may include a barrier structure, such as an end cap orseal, configured to maintain the fluid inside the tube until asufficient pressure from the inflation of the gas chamber(s) ruptures,disengages, or otherwise removes, the barrier structure, such that thefluid can be dispensed.

In one embodiment, as shown in FIG. 5B, the tube 538 is sized to extendpast the cervix 534 of the subject in the extended position. That is,the tube 538 may be designed to have a length that extends from theintended vaginal implantation site past the cervix of the subject inwhich the device is to be implanted. In one embodiment, as shown inFIGS. 5A and 5B, the tube 538 is configured to have a coiled unstressedposition and the extended position is an uncoiled position. For example,each of the chambers may be inflated as gas is released from the gasreservoir and the chamber(s) expand thereby forcing the tubing touncoil. The gas released from the gas reservoir may also serve to drivethe fluid from the tube during or upon uncoiling of the tube.

For example, in devices having the extendable tube dispensing mechanism,the velocity of the fluid being dispensed may be lower than that offluid being dispensed from a device without such an extension tube,because the fluid is being dispensed past the cervix.

In certain embodiments, the tube may be coated with an anti-microbial oranti-wetting coating to prevent contaminants from flowing into the tubefrom the vaginal or uterine deployment site, or from one gas chamber toanother.

In one embodiment, the tube includes at least two gas chambers in seriesalong the tube that have a seal therebetween, such that the second gaschamber may only begin to inflate upon full or near full inflation ofthe first gas chamber of the tube.

In certain embodiments, a dispense tube is combined with the inkjet-typeor high-velocity dispense devices described above. That is, a tubeextending between the device and the cervix or uterus of a subject maybe provided, either independently of the device (e.g., the tube may beinserted into the subject prior to deployment of the device) or inassociation with the device (e.g., in connection with the dispensingnozzle or outlet of the device), to ensure delivery of the fluid to thedesired site, such as the uterus. Incorporation of such a tube into thedevice or system may decrease the required fluid velocity produced bythe dispensing mechanism, because the fluid is dispensed past the cervixvia the tube. In certain embodiments, the tube may be coated with ananti-microbial or anti-wetting coating to prevent contaminants fromflowing into the tube from the vaginal or uterine deployment site.

In one embodiment, as shown in FIG. 6 , an implantable fluid deliverysystem includes a device 600 having a housing 602 configured forintravaginal deployment and retention in a subject and a fluiddispensing mechanism 630 disposed within the housing 602. The device mayinclude any of the features, or combinations of features, describedherein. The system also includes a capsule 632 containing a fluid to bedelivered to the subject, the capsule 632 being configured to beinserted past the cervix 632 of the subject prior to deployment of thedevice 600. In one embodiment, the fluid dispensing mechanism 630includes an ultrasonic element configured to generate an ultrasonic waveeffective to rupture the capsule 632 and release the fluid to the uterusof the subject. For example, the capsule may be inserted past the cervixof the subject manually, for example by ranch personnel in the case ofcattle, or using a deployment device configured to deploy the capsulepast the cervix.

In one embodiment, the ultrasonic element comprises a piezoelectricmaterial and an acoustic horn.

Suitable device features, including housing designs, retention features,retrieval members, control system features, and additional fluiddispensing mechanisms (not configured for uteral delivery from anintravaginal device), are disclosed in application Ser. No. 13/629,124,filed on Sep. 27, 2012, entitled “Single Channel, Multiple Drug DeliveryDevice and Methods”, application Ser. No. 13/629,159, filed on Sep. 27,2012, entitled “Multiple Reservoir Drug Delivery Device and Methods”,application Ser. No. 13/629,184, filed on Sep. 27, 2012, entitled “DrugReconstitution and Delivery Device and Methods”, application Ser. No.13/742,203, filed on Jan. 15, 2013, entitled “Devices and Methods forIntraluminal Retention and Drug Delivery” (29833-0033), application Ser.No. 14/071,929, filed on Nov. 5, 2013, entitled “Fluid Delivery Devicesand Methods”, and application Ser. No. 14/107,367, filed on Dec. 16,2013, entitled “Electrolytic Gas Generating Devices, Actuators, andMethods”, each of which is incorporated herein by reference in itsentirety.

Advantageously, the devices and systems described herein provide forfluid dispensing to a site past the cervix, with a vaginally implanteddevice, thereby increasing the precision of the fluid delivery and thelikelihood of delivery to the uterus. Desirably, in IVF procedures,these devices and systems increase the efficiency and the likelihood ofsuccess of procedures, requiring less time and sperm per subject.

In certain embodiments, the devices described herein may be configuredto dispense the fluid when an estrus condition of the subject detectedby the device meets a predetermined threshold. That is, the device maybe configured to detect when the subject is displaying ideal or nearideal insemination conditions (i.e., estrus) and to dispense the fluidin response to the detection of estrus. Devices for detecting estrus aredescribed in more detail in co-pending application Ser. No. 14/448,074,filed on Jul. 31, 2014, entitled “Implantable Estrus Detection Devices,Systems, and Methods,” which is incorporated herein by reference in itsentirety.

In certain embodiments, the fluid includes drugs, semen, ova, orcombinations thereof.

In certain embodiments, the fluid delivery devices disclosed herein maybe configured to release two or more fluids therefrom, such as fromseparate reservoirs. For example, a device may be configured to dispensea series of drugs to the patient. For example, a device may beconfigured to dispense both an ova and semen to a patient.

Methods of Fluid Delivery

In another aspect, methods of delivering fluid to a subject areprovided. For example, the methods may include deploying a fluiddelivery device or system, such as those disclosed herein, in thesubject. The devices and systems may include any features, orcombinations of features, disclosed herein.

In one embodiment, a method of delivering fluid to a subject includesintravaginally deploying and retaining a device in the subject, anddispensing the fluid from the device such that the fluid is driven pastthe cervix to the uterus of the subject. For example, the device mayinclude at least one reservoir containing a fluid and a fluid dispensingmechanism.

In one embodiment, dispensing the fluid from the device includes heatinga portion of the fluid in a chamber to create a bubble such that adroplet of the fluid is dispensed via a nozzle upon expansion of thebubble.

In one embodiment, dispensing the fluid from the device includesproviding an electric charge to a piezoelectric material, therebycausing it to vibrate and drive a portion of the fluid from a chambersuch that the portion of fluid is dispensed from the device through anozzle.

In one embodiment, dispensing the fluid from the device includesgenerating pressure in the at least one reservoir to drive the fluidtoward a nozzle, and the device also includes a valve configured toallow flow of the fluid from the at least one reservoir to the nozzleupon generation of sufficient pressure in the at least one reservoir.For example, the pressure source may include compressed gases, asprings, pistons, and combinations thereof.

In one embodiment, the at least one reservoir includes a tube extendingfrom a gas reservoir of the device, which includes at least one gaschamber that is in fluid communication with the fluid contained in thetube, and the step of dispensing the fluid from the device includesinflating the at least one gas chamber of the tube with gas from a gasreservoir of the device, thereby urging the tube into an extendedposition and driving the fluid from the tube. For example, the tube maybe sized to extend past the cervix of the subject in the extendedposition. In one embodiment, the tube is configured to have a coiledunstressed position, and the extended position is an uncoiled position.

In certain embodiments, a method of delivering fluid to a subjectincludes inserting a capsule containing a fluid to be delivered to thesubject past the cervix of the subject, thereafter intravaginallydeploying a device in the subject, the device comprising a fluiddispensing mechanism, which comprises an ultrasonic element, andgenerating an ultrasonic wave, via the ultrasonic element, effective torupture the capsule and release the fluid to the uterus of the subject.In one embodiment, the ultrasonic element includes a piezoelectricmaterial and an acoustic horn.

In one embodiment, dispensing the fluid from the device such that thefluid is driven past the cervix to the uterus of the subject occursafter an estrus condition of the subject detected by the device meets apredetermined threshold. For example, the fluid may include drugs,semen, ova, and combinations thereof. In a particular embodiment, thesubject is a horse, cow, sheep, or sow. In another embodiment, thesubject is a woman.

It will be appreciated that variants of the above-disclosed and otherfeatures and functions, or alternatives thereof, may be combined intomany other different devices, systems, methods, or applications. Variouspresently unforeseen or unanticipated alternatives, modifications,variations, or improvements therein may be subsequently made by thoseskilled in the art which are also intended to be encompassed by thefollowing claims.

We claim:
 1. An implantable fluid delivery system, comprising: a devicecomprising a housing configured for intravaginal deployment andretention in a subject and a fluid dispensing mechanism disposed withinthe housing; and a capsule containing a fluid to be delivered to thesubject, the capsule being configured to be inserted past the cervix ofthe subject prior to deployment of the device, wherein the fluiddispensing mechanism comprises an ultrasonic element configured togenerate an ultrasonic wave effective to rupture the capsule and releasethe fluid to the uterus of the subject.
 2. The system of claim 1,wherein the ultrasonic element comprises a piezoelectric material and anacoustic horn.
 3. The system of claim 1, wherein the device isconfigured to dispense the fluid when an estrus condition of the subjectdetected by the device meets a predetermined threshold.
 4. The system ofclaim 1, wherein the fluid is selected from the group consisting ofdrugs, semen, ova, and combinations thereof.
 5. The system of claim 4,wherein the fluid comprises a combination of drugs.
 6. The system ofclaim 4, wherein the fluid comprises a combination of two or more ofdrugs, semen, and ova.
 7. The system of claim 1, wherein the devicecomprises a power source, a microcontroller, and an activationmechanism.
 8. The system of claim 1, wherein the subject is one of ahorse, cow, sheep, and sow.
 9. The system of claim 1, further comprisinga deployment device configured to insert the capsule past the cervix ofthe subject.
 10. A method of delivering fluid to a subject, comprising:inserting a capsule containing a fluid to be delivered to the subjectpast the cervix of the subject; thereafter intravaginally deploying adevice in the subject, the device comprising a fluid dispensingmechanism, which comprises an ultrasonic element; and generating anultrasonic wave, via the ultrasonic element, effective to rupture thecapsule and release the fluid to the uterus of the subject.
 11. Themethod of claim 10, wherein the ultrasonic element comprises apiezoelectric material and an acoustic horn.
 12. The method of claim 10,wherein generating an ultrasonic wave occurs in response to the devicedetecting an estrus condition of the subject meeting a predeterminedthreshold.
 13. The method of claim 10, wherein the fluid is selectedfrom the group consisting of drugs, semen, ova, and combinationsthereof.
 14. The method of claim 13, wherein the fluid comprises acombination of drugs.
 15. The method of claim 13, wherein the fluidcomprises a combination of two or more of drugs, semen, and ova.
 16. Themethod of claim 1, wherein the subject is one of a horse, cow, sheep,and sow.
 17. The method of claim 10, wherein inserting the capsulecomprises activating a deployment device configured to insert thecapsule past the cervix of the subject.